In PCT/GB02/00620 the applicant discloses a method of preparing a herbal drug extract (botanical drug substance) from medicinal cannabis. The process comprises:    1. a heating step to decarboxylate the acid form of the cannabinoids to their neutral form;    2. a first extraction with a specified volume of liquid carbon dioxide for 6–8 hours; and    3. a step to reduce the proportion of non-target materials, referred to as winterisation, which step precipitates out waxes.
More specifically, PCT/GB02/00620 describes a process wherein:    step 1 comprises heating chopped cannabis (2–3 mm) at 100–150° C. for sufficient time to allow decarboxylation;    step 2 comprises CO2 extraction using:    a) a coarse powder (the particles are passed through a 3 mm mesh);    b) a packing density of 0.3; and    c) supercritical conditions of 600 bar at 35° C. for 4 hours, although other combinations of temp and pressure ranging from 10–35° C. and 60–600 bar (both super critical and sub critical conditions) could, it is acknowledged, be used; and    step 3 comprises conducting an ethanolic precipitation at −20° C. for 24 hours and removing the waxy material by filtration.
The supercritical method disclosed in PCT/GB02/00620 produced:    a) a high THC extract containing:    60% THC (Δ9-tetrahydrocannabinol)    1–2% CBD (cannabidiol)    4–5% other minor cannabinoids including CBN (cannabinol)    (Quantative yields were 9% wt/wt based on dry weight of medicinal cannabis); and    b) a high CBD extract containing:    60% CBD    4% THC    2% other cannabinoids    (Quantative yields were 9% wt/wt based on dry weight of medicinal cannabis).
Clearly as the resulting BDS is to be used in a pharmaceutical product it is essential that the process is safe, scalable to GMP and gives high degrees of product consistency and, preferably also good yields.
The principles of supercritical fluid extraction (SFE) have been known since the work of Baron Cagniard de le Tour in 1822 when it was noted that the gas-liquid boundary disappeared when the temperature of certain materials was increased by heating them in a closed glass container. From this early work the critical point of a substance was first discovered. The critical point is the temperature above which a substance can co-exist in gas, liquid and solid phases. It was later found that by taking substances to or above their critical temperature and pressure they could be used as sophisticated solvents for extraction and fractionation of complex mixtures.
The technique is widely used in the fuel oil processing business and has been applied to, for example, the purification and separation of vegetable and fish oils.
An attractive feature of SFE over the use of conventional solvents is that the solvent power (E°) can be varied by manipulation of temperature and pressure above the critical point.
In a typical pressure-temperature diagram for a substance there are three lines which define the equilibrium between two of the phases. These lines meet at the triple point. The lines define the interface between gas, liquid and solid states, and points along the line define the equilibrium between pairs of phases. For example, the vapour pressure (boiling point) curve starts at the triple point and ends at the critical point. The critical region starts at this point and a supercritical fluid is any substance that is above its critical temperature (Tc) and critical pressure (Pc). The critical temperature is thus the highest temperature at which a gas can be converted to a liquid by an increase in pressure and the critical pressure is the highest pressure at which a liquid can be converted into a traditional gas by increasing the temperature. In the so-called critical region, there is only one phase and it possesses some of the properties of both a gas and a liquid.